Early peripheral B cells in inactive SLE are transcriptionally and epigenetically primed for T-dependent activation
Journal of Immunology(2023)
摘要
Abstract Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterized by repeated episodes of increased disease activity followed by periods of inactivity and remission. Increased titer of anti-dsDNA autoantibodies is often associated with active disease and the proliferation of autoreactive B cells are thought to play a major role in the progression of disease. In this study we investigated the transcriptional and epigenetic profile of early peripheral B cells—transitional (T1T2) and resting naïve (rN)—in inactive and active disease from a large cohort (n=46) of African American SLE patients. Our results show that the transcriptome of these B cells show a dysregulated signature as previously reported, but this signature is distinct between inactive and active SLE. Active disease is characterized by a greater number of differentially expressed genes (DEG) compared to healthy controls (HC), however, rN B cells in inactive disease patients express high levels of genes associated with T-dependent activation, IL4 signaling, and germinal center reactions. Chromatin accessibility across the genome of inactive disease B cells show that they share a subset of differentially accessible regions (DAR) from HC that are similarly dysregulated in both inactive and active flaring individuals, but inactive SLE B cells also have acquired several hundred unique DAR regions—some of which correspond with motifs or loci encoding important B cell development transcription factors. These findings suggest a distinct profile in early B cells from inactive disease patients that remains present during disease remission and may predispose these cells towards T-dependent activation as a response to long-term disease. Supported by grants from NIH (T32 GM0008490, 3U19 AI110483-08S2 8744)
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关键词
inactive sle,activation,t-dependent
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